Chemoprevention of DMBA-induced UV-B promoted, NOR-1-induced TPA promoted skin carcinogenesis, and DEN-induced phenobarbital promoted liver tumors in mice by extract of beetroot

Department of Pharmaceutical Sciences, School of Pharmacy, Howard University, 2300 4th Street, NW, Washington, DC 20059, USA.
Pharmacological Research (Impact Factor: 4.41). 03/2003; 47(2):141-8. DOI: 10.1016/S1043-6618(02)00285-2
Source: PubMed


Our previous studies identified the extract of Beta vulgaris (beetroot), commercially also known as betanin, as a potent cancer chemopreventive agent in both in vitro Epstein-Barr early antigen activation assay and in an in vivo two-stage mouse lung and skin carcinogenesis. To explore this issue further, we have now investigated its cancer chemopreventive potentials in three different chemical carcinogen initiation-promotion experimental tumor models in mice. Following tumor initiation with 390 nmol of 7,12-dimethylbenz(a)anthracene (DMBA) in 100 microl of acetone, the mouse skin tumor promotion with 3430 J/m(2) of ultraviolet light-B (UV-B) as well as splenomegaly was significantly inhibited by oral administration of 0.0025% betanin. At the same dose, betanin also afforded significant protection in the mouse skin cancer model following the topical application of 390 nmol of (+/-)-(E)-4-methyl-2-[(E)-hydroxyamino]-5-nitro-6-methoxy-3-hexanamide (NOR-1) in 100 microl of acetone and promoted by topical administration of 1.7 nmol of 12-O-tetradecanoylphorbol-13-acetate (TPA). In the two-stage model of hepatocarcinogenesis in mice with N-nitrosodiethylamine (DEN, 30 mg/kg) as the initiator and phenobarbital as the promoter, oral administration of 0.0025% betanin also showed a very significant inhibition of both the incidence and multiplicity of the liver tumors. These findings along with our initial reports suggest that betanin which is a regularly consumed natural product colorant is an effective cancer chemopreventive agent in mice. The most interesting observation is that the cancer chemopreventive effect was exhibited at a very low dose used in the study and thus indicating that beetroot warrants more attention for possible human applications in the control of malignancy.

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    • "They may bind carcinogens and thereby reduce their transfer through cell membranes into cells. This in turn decreases the intensity of reactions catalyzed by enzymes such as monooxygenases and hydrases (Kapadia et al., 2003). Apart from betalains red beetroots contain also other biologically active compounds such as vitamin C, which also has antioxidant properties, and folic acid, protecting nucleic acids from aberrations of genes responsible for predisposition to certain types of cancer , e.g. "
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    ABSTRACT: The aim of the study was to investigate the effects of beetroot juice fermented by Lactobacillus brevis 0944 and Lactobacillus paracasei 0920 (FBJ) on carcinogen induction of aberrant crypt foci (ACF) in rat colon. 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) was used as carcinogen, which was administrated intragastrically at a dose of 10μg/day, every day of the experiment. Additionally, we investigated the cytotoxicity and genotoxicity of fecal water from experimental animals in the Caco-2 cell line, evaluated by MTT test and the comet assay, respectively, as well as by the count of bacteria adhered to colon epithelium assessed by fluorescence in situ hybridization. Oxidative stress in rats was expressed by measuring serum antioxidant status and the level of malondialdehyde in the kidneys and liver. The experimental rats were divided into four groups based on diet type: basal diet, basal diet supplemented with FBJ, basal diet and PhIP treatment, and basal diet supplemented with FBJ and PhIP treatment. FBJ significantly reduced the number of ACF in PhIP-treated rats (from 59±18 to 26±4). Moreover, the number of extensive aberrations (more than 4 crypts in a focus) decreased from 52±18 to 18±4. Fecal water obtained from rats fed with a PhIP-containing diet induced pronounced cytotoxic and genotoxic effects in Caco-2 cells, but FBJ supplementation of the diet abolished these effects. In groups fed dietary PhP and FBJ the latter was found to increase the antioxidant status of serum from 40% to 66% depending on the fraction. Reduced concentration of malondialdehyde was found only in the kidneys of rats fed with PhIP and FBJ. FBJ present in the diet of rats causes a reduction of MDA in the kidneys from 118.7nmol/g tissue to 100nmol/g tissue. The presence of FBJ in the diet of rats significantly increased the count of bacteria, including Lactobacillus/Enterococcus and Bacteroides-Prevotella group adhered to colonic epithelium. In conclusion, supplementation of the diet with lactofermented beetroot juice may provide protection against precancerous aberrant crypt formation and reduce the cytotoxic and genotoxic effects of fecal water and improve the oxidative status of the organism.
    09/2012; 34(3). DOI:10.1016/j.etap.2012.08.009
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    • "rubra) is a common ingredient of the traditional diet, particularly in Central and Eastern Europe. Beetroot extract was identified as a potent cancer chemopreventive agent inhibiting the 7,12-dimethylbenz[a]anthracene initiated tumorigenesis in mouse skin and diethylnitrosamine induced mouse hepatocarcinogenesis (Kapadia et al., 2003). It was shown also that pretreatment of rats with beetroot juice can counteract, to some extent, xenobiotic-induced oxidative stress (Kujawska et al., 2009). "
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    ABSTRACT: The aim of this study was to evaluate the effect of betanin, one of the beetroot major components, on ROS production, DNA damage and apoptosis in human resting and stimulated with phorbol 12-myristate13-acetate polymorphonuclear neutrophils, one of the key elements of the inflammatory response. Incubation of neutrophils with betanin in the concentration range 2–500 µm resulted in significant inhibition of ROS production (by 15–46%, depending on the ROS detection assay). The antioxidant capacity of betanin was most prominently expressed in the chemiluminescence measurements. This compound decreased also the percentage of DNA in comet tails in stimulated neutrophils, but only at the 24 h time point. In resting neutrophils an increased level of DNA in comet tails was observed. Betanin did not affect the activity of caspase-3, in resting neutrophils, but significantly enhanced the enzyme activity in stimulated neutrophils. The western blot analysis showed, however, an increased level of caspase-3 cleavage products as a result of betanin treatment both in resting and stimulated neutrophils. The results indicate that betanin may be responsible for the effect of beetroot products on neutrophil oxidative metabolism and its consequences, DNA damage and apoptosis. The dose and time dependent effects on these processes require further studies. Copyright
    Phytotherapy Research 06/2012; 26(6):845-52. DOI:10.1002/ptr.3649 · 2.66 Impact Factor
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    • "Lu and co-authors [35] found that the oral administration of betalains from red beets (5, 20 or 80 mg/kg BW) in irradiated mice significantly enhanced the activity of SOD and GPx in the liver, spleen and kidney in a dose-dependent manner. In three different experimental tumour models in mice, Kapadia [36] reported that a very low dose of betanin (0.0025%) from beetroot acts as a potent chemopreventive agent. "
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    ABSTRACT: The objective of the present study was to examine the influence of adding various amounts beetroot (Beta vulgaris) crisps on gastrointestinal function, antioxidant status and blood and liver lipid profiles in a high fat diet-induced dyslipidaemic rat model; The intake of a dyslipidaemic diet increased the serum total cholesterol, total cholesterol-to-HDL-cholesterol ratio, atherogenic index, hepatic total cholesterol and triacylglycerols, suppressed production of short-chain fatty acids and decreased total antioxidant status and blood glutathione peroxidase activity. Oral administration of all tested amounts of beetroot crisps prevented the rise in serum total cholesterol and triacylglycerols levels. The treatment with the addition of 3% crisps also decreased hepatic total cholesterol level and activity of AST in serum. The experimental addition of crisps likewise resulted in a tendency towards a higher total SCFA pool and activity of glutathione peroxidase and a lower serum glucose level (p = 0.080, p = 0.061 and p = 0.067, respectively); Results of the presented study suggest that the addition of beetroot crisps could alleviate metabolic changes in dyslipidaemic diet-administered rats.
    Lipids in Health and Disease 10/2011; 10(1):178. DOI:10.1186/1476-511X-10-178 · 2.22 Impact Factor
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